Method and device for administering a humidified aerosol to a patient interface

ABSTRACT

A method and device are used for administering a humidified aerosol to a patient interface by providing and guiding a first gas flow having a humidified aerosol, a second gas flow having humidified respiratory gases, and a liquid flow of a thermally balancing liquid, thermally balancing the first and second gas flow by parallel guiding the first and second gas flow such that the first and second gas flow are guided in a manner that they are at least partially surrounded by the liquid flow of the thermally balancing liquid, mixing the first and second gas flow to obtain enriched respiratory gases having the humidified aerosol, and administering the enriched respiratory gases to the patient interface. The method and the device avoid the administration of dry or re-dried powdered aerosols and unwanted accumulation of and blockage by powdered material. The device is useful in respiratory support of preterm infants.

FIELD OF THE INVENTION

The present invention relates to a method, a device and a use thereoffor administering a humidified aerosol to a patient interface. Moreparticular, the method and the device may be designed for providingenriched respiratory gases comprising the humidified aerosol to thepatient interface.

RELATED ART

As for example described in WO 2015/132172 A1, a dry material, alsodenotable as “aerosolizable material”, which comprises particles of apowdered substance, preferably a pharmaceutical preparation, is treatedin an aerosolization device by a compressed carrier gas in order toentrain the particles into a gas stream which are hereby converted tothe desired aerosol, also denominated as “powdered aerosol”. In thisstate, the particles of the dry material are distributed across theentire volume of the carrier gas, preferably in a uniform and finelydispersed form.

Such kinds of devices are, typically, used for inhalative administrationof pharmaceutical preparations to patients which are breathing normally,to mechanically ventilated patients or to patients who are underventilatory support. For normally breathing patients, typical examplesinclude handheld dry powder inhalers or metered dose inhalers. Forpatients who are subject to mechanical ventilation or ventilatorysupport, a ventilatory circuit is used. For this purpose, a patientinterface is integrated into, or attached to, the ventilatory circuit,wherein the ventilatory circuit, in general, comprises a ventilator andtubes adapted for guiding gases from the ventilator to a patientinterface and back. In particular, a suitable mouthpiece, a breathingmask, a nasal cannula or a tracheal cannula are part of the patientinterface or attachable thereto. A continuous inhalative administrationof liquid aerosols can nowadays be considered as standard therapy forventilated patients in intensive care units.

Pharmaceutical preparations can be administered in form of an inhalabledry powder by using dry powder inhalers, as for example disclosed infrom US 2010/006095 A1. However, an inhalation of powdered aerosols, inparticular of hygroscopic powdered aerosols, may result in intolerance,incompatibility or other adverse reactions, especially in the oralmucosa. As described in G. Pohlmann et al., A Novel Continuous PowderAerosolizes (CPA) for Inhalative Administration of Highly concentratedRecombinant Surfactant Protein-C (rSP-C) Surfactant to Preterm Neonates,JAMP, Vol. 26, No. 6, 2013, the administration of dry powdered aerosolsinto the ventilatory circuit and the respiratory tract which are bothhumid may result in a considerable unwanted deposition of powderedmaterial, which may, finally, lead to a blockage of a tube or of anairway in the respiratory tract. These blockages may, thus, result inconsiderable obstructions in breathing for the patient up tosuffocation. In particular small cross sections, such as the small crosssections which are, typically, used in respiratory support of preterminfants, comprise a high risk of suffocation. In addition, such unwanteddeposition may render it difficult or even impossible to determine theexact dose of a substance to be administered which may have actuallyreached the target organ.

WO 2015/132172 A1 discloses a humidifier which is configured to humidifyan aerosol. In particular by adjusting the temperature a thin liquidfilm is generated on surfaces of the previously dry particles. Asresult, dry particles which would otherwise be deposited on walls of thedevice or on the oral mucosa can simply be drained off by using thisthin liquid film. Herein, the humidifier may be used in connection withan aerosolization device and the humidified aerosol may be provided to apatient who is either an actively breathing patient or a mechanicallyventilated patient.

US 2014/216446 A1 discloses a device for providing a breathing gasstream, which contains a therapeutically active substance, for themechanical respiration and/or mechanical breathing assistance of apatient. Herein, the device has at least one first line, through which afirst gas stream flows during the operation of the device, and at leastone second line, wherein the first line and the second line have acommon section and are connected to one another by a watervapor-permeable membrane in the area of the common flow section.Further, a second gas stream to flow through the second line during theoperation of the device is provided.

WO 2012/025496 A1 relates to aerosolized and humidified particlescomprising a therapeutically active substance which can be obtained bysuspending dry inhalable particles in a carrier gas, adding water vaporand causing condensation of water on the particles. Further, methods togenerate these particles and an apparatus useful to carry out suchmethods are disclosed therein.

In addition, WO 2008/030592 A2, WO 2014/095858 A1, U.S. Pat. No.5,031,612 A, and GB 2 465 358 A disclose methods and devices whichcontribute to a technological background to the present invention.

PROBLEM TO BE SOLVED

However, even diligently humidifying the aerosol particles may not besufficient of avoiding an effect that the humidified aerosol particlesmay be subject to a subsequent partial redrying, such as by an incidenceof heat, especially of solar radiation.

It is therefore an objective of the present invention to provide amethod and a device for administering a humidified aerosol to a patientinterface which at least partially avoids this problem. Consequently, itwould be desirable to engage a method and a device which would allowkeeping the aerosol particles in a humidified state during their wholeadministration.

SUMMARY OF THE INVENTION

This problem is solved by a method, a device and a use thereof foradministering a humidified aerosol to a patient interface having thefeatures of the independent claims. Preferred embodiments, which mightbe implemented in isolated fashion or in any arbitrary combination, aresubject matter of the dependent claims.

As used in the following, the terms “have”, “comprise” or “include” orany arbitrary grammatical variations thereof are used in a non-exclusiveway. Thus, these terms may both refer to a situation in which, besidesthe feature introduced by these terms, no further features are presentin the entity described in this context and to a situation in which oneor more further features are present. As an example, the expressions “Ahas B”, “A comprises B” and “A includes B” may both refer to a situationin which, besides B, no other element is present in A (i.e. a situationin which A solely and exclusively consists of B) and to a situation inwhich, besides B, one or more further elements are present in entity A,such as element C, elements C and D or even further elements.

Further, as used in the following, the terms “preferably”, “morepreferably”, “particularly”, “more particularly”, “specifically”, “morespecifically” or similar terms are used in conjunction with optionalfeatures, without restricting alternative possibilities. Thus, featuresintroduced by these terms are optional features and are not intended torestrict the scope of the claims in any way. The invention may, as theskilled person will recognize, be performed by using alternativefeatures. Similarly, features introduced by “in an embodiment of theinvention” or similar expressions are intended to be optional features,without any restriction regarding alternative embodiments of theinvention, without any restrictions regarding the scope of the inventionand without any restriction regarding the possibility of combining thefeatures introduced in such way with other optional or non-optionalfeatures of the invention.

In a first aspect, the present invention refers to a method foradministering a humidified aerosol to a patient interface.

As used herein, the term “powdered aerosol” refers to an aerosolizablematerial that comprises particles of a powdered substance which aresuspended in a gas phase, wherein the particles may, in particular, beor comprise particles of a pharmaceutical preparation, such as, forexample, a lung surfactant. For converting the particles into thisstate, the aerosolizable material has been treated in an aerosolizationdevice by a compressed carrier gas in order to entrain the particlesinto a gas stream. In this state, the particles of the dry material are,preferably, distributed across the entire volume of the carrier gas, inparticular, in a uniform and finely dispersed form.

As further used herein, the term “humidified aerosol” refers to apreviously dry powdered aerosol that comprised previously dry particleswhich has been treated in a manner to generate humidified particles.Herein, the humidified aerosol may exhibit a high degree of relativehumidity, preferably at least 50% relative humidity, more preferred atleast 130% relative humidity, in particular, of 100% relative humidity,for a temperature at which the present method may be applied.Preferably, this temperature may be close to a body temperature, such asbetween 30° C. and 42° C. As mentioned above, known and device methodsexist, such as the method and the humidifier of WO 2015/132172 A1, whichmay be applied for generating a humidified aerosol.

As generally used, the term “relative humidity” refers to a relativeamount of water vapor being present in a mixture of water vapor and thecarrier gas, such as in the respiratory gases. Thus, the relativehumidity of the mixture, which may, preferably, be expressed as apercent value, typically indicates a ratio of water vapor with respectto the saturation humidity for a given temperature. Herein, water vapormay condensate onto the surfaces of the aerosol particles at a relativehumidity above 100% whereas water being bound at the surfaces of theaerosol particles may vaporize at a relative humidity below 100%.

Consequently, a dynamic equilibrium between water in form of vapor andwater bound at the surfaces of the aerosol particles exists at 100%relative humidity, wherein, in practice, the dynamic equilibrium existsin a range around 100% relative humidity as known by the skilled person.Further, by feeding a cool humidified aerosol into the mixture anincrease of the evaporation of water vapor from the surfaces of theaerosol particles may occur, thus, resulting in a redrying of theparticles.

Further, the term “ventilatory circuit” refers to a device beingconfigured for a ventilation of respiratory gases as provided by aventilator to a patient and from the patient back to the ventilator,hereby excluding the respiratory tracks of the patient. As used herein,the term “patient” may, in particular, refer to a human being of anyage, in particular, including preterm infants. Further, the term“ventilation” relates to a process of accomplishing a movement of therespiratory gases, in particular, via alternating steps of inhalationand exhalation. In contrast to normally breathing patients who arecapable of performing the circulation without any additional aids,patients who are subject to mechanical ventilation, require therespiratory gases at least partially to be provided from the ventilatorvia the ventilatory circuit. As used herein, the term “patientinterface” refers to a unit being configured for providing a connectionbetween the ventilatory circuit and the respiratory track of the patientwhich is therefore, in general, located adjacent to the patient. Forthis purpose, the patient interface may be integrated into, or attachedto, the ventilatory circuit, wherein the ventilatory circuit may, ingeneral, comprise a ventilator and tubes adapted for guiding gases fromthe ventilator to a patient interface and back. In particular, asuitable mouthpiece, a breathing mask, a nasal cannula or a trachealcannula may be part of the patient interface or attachable thereto.However, other arrangements of the patient interface may also befeasible.

As generally known, the respiratory gases may, in addition, act as acarrier gas that can, preferably, be enriched by the humidified aerosol,thus, resulting in a process which may be described by the phrase“administering the humidified aerosol”. Herein, the term “administering”refers to a process of allowing a controlled application of therespiratory gases and the humidified aerosol comprised hereby, inparticular, by providing a predefined amount of the pharmaceuticalpreparation as comprised by the humidified aerosol per time period. Asused herein, the term “respiratory gases” refers to a gas mixture whichcomprises a composition being suitable for the ventilation of a patient,in particular, air or oxygen-enriched air.

Investigations with humidified aerosols have revealed that thehumidified previously dry aerosol particles may be subject to a partialredrying, such as by an incidence of heat, especially of solarradiation. However, other reasons for causing a drying of the aerosolmay also occur. In particular, the heat may cause an increase oftemperature in the ventilatory circuit in a manner that the temperatureof the completely humidified aerosol, which has been provided at 100%relative humidity, may increase. As described above, the humidifiedaerosol may gradually lose water at increasing temperatures, thus,leading to a successively drying of the aerosol. The administration ofthe successively more and more dried powdered aerosol may, thus, similarto the case of administration of a dry aerosol, result in a considerableamount of deposited powdered material, which may, finally, lead to ablockage of a tube or an airway in the respiratory tract. This resultmay, particularly, be due to the fact that deposited dry powder cannotrinse away. As already indicated above, these blockages may, thus,result in considerable obstructions in breathing up to suffocation ofthe patient.

Alternatively or in addition, even when a first flow of a 100%humidified aerosol and a second flow of 100% humidified carrier gas areseparately guided until they are mixed into a mixture at a mixingchamber which may be located adjacent to the patient interface, asimilar effect may be observable when the separately guided flows mayexhibit a different temperature. In this case, it may rather be likelythat the common temperature of the mixture in the mixing chamber mayrise above a dew point of the mixture, thus, resulting in a loss ofwater of the surface of the particles. This effect may, especially, bedangerous in nasal prongs which are, typically, used in the respiratorysupport of preterm infants since they comprise particularly small crosssections, thus, leading to a high risk of suffocation of the infant.

As a result, when a gaseous flow which exhibits 100% relative humidityis cooled along a pathway, the relative humidity of this stream mayalways assume 100% along the pathway as long as vapor which has becomeredundant due to the decreasing temperature may be deposited onavailable surfaces. Further, when two of such flows, wherein the firstflow may comprise the enriched carrier gas with the humidified aerosoland the second flow the respiratory gases, may be mixed, it can beparticularly advantageous when the temperatures of the flows are thesame at their arrival in the mixing chamber since 100% relative humidityis retained in this case. As a result, no redrying of the aerosolparticles may occur. It is, thus, proposed to thermally balance the twoflows prior to their mixing. In addition, a liquid flow comprising athermally shielding against environmental heating or cooling andapplying a constant temperature gradient along the gas pathways isapplied in order to be able to also achieve the desired thermallybalancing between the first flow and the second flow.

The method for administering a humidified aerosol to a patientinterface, thus, comprises the following steps a) to f):

-   -   a) providing and guiding a first gas flow comprising a        humidified aerosol;    -   b) providing and guiding a second gas flow comprising humidified        respiratory gases;    -   c) providing and guiding a liquid flow of a thermally balancing        liquid;    -   d) thermally balancing the first gas flow and the second gas        flow by parallel guiding the first gas flow and the second gas        flow, wherein the first gas flow and the second gas flow are        guided in a manner that they are at least partially surrounded        by the liquid flow of the thermally balancing liquid;    -   e) mixing the first gas flow and the second gas flow, whereby        enriched respiratory gases comprising the humidified aerosol are        obtained; and    -   f) administering the enriched respiratory gases comprising the        humidified aerosol to the patient interface.

Herein, although the indicated steps may be performed in the givenorder, wherein, preferably, all of the indicated steps may be preformedat least partially concurrently. Further, additional method steps,whether described in this document or not, may be performed, too.

According to steps a) and b), each of the first gas flow comprising thehumidified aerosol and of the second gas flow comprising the humidifiedrespiratory gases are provided and guided, preferably separatelyprovided and separately guided, wherein, according to step d), the firstgas flow and the second gas flow are thermally balanced, particularlyprior to step e), by parallel guiding the first gas flow and the secondgas flow. In a particularly preferred embodiment in which the first gasflow comprising the humidified aerosol may exhibit a smaller flow volumecompared to the second gas flow comprising the humidified respiratorygases, the second gas flow may be guided in a manner that it may atleast partially, preferably fully in a lateral direction of the flow,surround the first gas flow. However, other arrangements may also befeasible.

According to step c), the thermal balancing of the first flow and of thesecond flow is supported by the liquid flow of the thermally balancingliquid which is separately provided and separately guided in a mannerthat it may at least partially, preferably fully in a lateral directionof the flow, surround both the first gas flow and the second gas flow.In particular, the liquid flow may be applied in form of a counter flowarrangement, thus, increasing an effectivity of the thermal balancing.Herein, the term “counter flow” refers to an arrangement in which theliquid flow may assume an opposite direction compared to the directionsof the first flow and of the second flow. However, a parallel flow ofthe first gas flow, the second gas flow and the liquid flow may also befeasible. As used herein, the term “thermally balancing liquid” refersto a liquid substance which is, generally, adapted for being used as asupport in achieving a thermal balance between to the first flow and ofthe second flow. In this regard, the liquid flow may be configured forshielding of the aerosol and the respiratory gases against heat ingressfrom the surrounding. Consequently, the liquid flow may comprise aliquid which may, preferably, exhibit a high heat capacity. For thispurpose, the thermally balancing liquid may, preferably, be selectedfrom one of water or an aqueous solution. However, other kinds ofliquids, such as a non-aqueous liquid or a non-aqueous solution can alsobe used.

In a particularly preferred embodiment, the liquid flow of the thermallybalancing liquid may be guided by applying a lower pressure in flowdirection, such as by using a pumping unit which may be adapted forapplying a lower pressure at the liquid flow, thus, being able to suckthe thermally balancing liquid instead of pressing it. This arrangementmay help avoiding that the thermally balancing liquid, i.e. the water orthe aqueous solution, may intrude into the first gas and/or the secondgas flow which is subject to be administered to the patient interfaceaccording to step f). As a consequence of this embodiment, a lowerpressure may be generated in the liquid flow, thus, inhibiting anintrusion of the thermally balancing liquid into the ventilatory circuitwhich may, otherwise, result in a suffocation of the patient.

The liquid flow may, in particular, be configured for shielding both thefirst flow and the second flow from any ambient influence as far aspossible, thus, allowing a considerably accurate setting of the commontemperature of the mixture generated by the first flow and of the secondflow. For this purpose, the first gas flow may be provided during stepa) at a first temperature, wherein the second gas flow may be providedduring step b) at a second temperature, whereas the first gas flow andthe second gas flow are guided according to step d) in a manner thatthey can be mixed during to step e) at a common temperature. Herein, thecommon temperature used for the mixing of the first gas flow and of thesecond gas flow may, preferably, be both lower than the firsttemperature and the second temperature. In a particularly preferredembodiment, the common temperature may, additionally, be adjusted to atemperature, in particular within a range ±1° C., preferably of ±0.5°C., more preferred of ±0.3° C., that can be determined for a breath ofthe patient, such as by using a thermometer or a thermocouple. However,other methods for determination of the temperature may also be feasible.As a result of this accurately adjusted temperature, a redrying of thehumidified aerosol during their mixing may practically be avoided, thus,additionally inhibiting a blockage of the patient interface. Inaddition, it may, particularly, be preferred when the first gas flow andthe second gas flow may be mixed during step e) in a manner that theresulting mixture also comprises 100% relative humidity.

According to step f), the enriched respiratory gases comprising thehumidified aerosol, preferably exhibiting 100% relative humidity, may,thus, be administered to the patient interface, hereby allowing thecontrolled application of the enriched respiratory gases which comprisethe humidified aerosol, in particular, by providing the respiratorygases together with a predefined amount of the pharmaceuticalpreparation comprised by the humidified aerosol per time period,practically without any lasting deposition of re-dried aerosols in thedevice according to the present invention.

As further mentioned above, both the first gas flow and the second gasflow may be provided at 100% relative humidity during step a) or stepb), respectively. For this purpose, a previously dry aerosol may behumidified prior to step a) while previously dry respiratory gases maybe humidified prior to step b), in particular by applying a firsthumidifier for the dry aerosol and a second humidifier for the dryrespiratory gases. As used herein, the term “dry” with respect to thedry aerosol and the dry respiratory gas may refer to a condition of theaerosol and of the respiratory gases comprising less than 100% relativehumidity, thus, allowing them to incorporate more water vapor to be atleast further humidified.

In a further aspect, the present invention refers to a device foradministering a humidified aerosol to a patient interface. Accordingly,the device comprises:

-   -   at least one first tube for receiving and guiding a first gas        flow comprising a humidified aerosol;    -   at least one second tube for receiving and guiding a second gas        flow comprising humidified respiratory gases;    -   at least one third tube for receiving and guiding a liquid flow        comprising a thermally balancing liquid;        wherein the first tube, the second tube and the third tube are        provided in a coaxial arrangement with respect to each other,        wherein the third tube covers the first tube and the second        tube; and    -   at least one mixing chamber for receiving and mixing the first        gas flow and the second gas flow and obtaining enriched        respiratory gases comprising the humidified aerosol, the mixing        chamber having at least one outlet for administering the        enriched respiratory gases comprising the humidified aerosol.

As used herein, the term “tube” refers to a hollow, elongated objectwhich is configured for receiving and guiding a flow of a gas and/or ofa liquid. Herein, any one or each of the tubes as mentioned herein maybe a rigid tube, such as a pipe, or, preferably, a semi-rigid or, morepreferred, a flexible tube, such as a hose or a sleeve. In this manner,by using the flexible tube, the device according to the presentinvention could, advantageously, more easily be adjusted to therequirements of the patient. In order to allow a substantially constantliquid or gas flow through the tube, thereby reducing a risk of possibledepositions, any one or each tube may, thus, comprise a substantiallyconstant cross section along their length.

Further, each of the tubes may have an axis, wherein the axis of two or,preferably, of all three different tubes may coincide with respect toeach other, thus, providing a triaxial arrangement of the first tube,the second tube and the third tube. Herein, the third tube may,preferably, cover the first tube and the second tube, in particular, inform of a jacket or a sheath covering both the first tube and the secondtube. This kind of arrangement may, in particular, be advantageous, inorder to achieve an effective cooling of both the first gas flow and thesecond gas flow inside their respective tubes. In a particularlypreferred embodiment, in which the first tube configured for receivingand guiding the humidified aerosol may exhibit a smaller flow volumecompared to the second tube configured for receiving and guiding thehumidified respiratory gases, the first tube may be located inside thesecond tube, thus, allowing the second gas flow at least partially,preferably fully, surrounding the first gas flow. In this particularlypreferred embodiment, it may be sufficient that the third tube maydirectly cover only the second tube since the second tube already coversthe first tube being located inside the second tube. However, otherarrangements may also be feasible, especially, when more than one firsttube and/or more than one second tube and/or more than one third tubemay be employed.

While the first tube is configured for receiving and guiding a first gasflow comprising a humidified aerosol, the second tube is configured forreceiving and guiding a second gas flow comprising humidifiedrespiratory gases. In a particular embodiment, the device may, thus,further comprise at least one first humidifier being configured forhumidifying dry aerosol and at least one second humidifier beingconfigured for humidifying dry respiratory gases. Herein, one or both ofthe humidifiers may be selected according to the disclosure of WO2015/132172 A1. However, other arrangements and other kinds ofhumidifiers may also be feasible.

In a further preferred embodiment in which the third tube may comprisean inlet for receiving the thermally balancing liquid and an outlet fordispensing the thermally balancing liquid, the device may furthercomprise a pumping unit which may be configured for applying a lowerpressure at the outlet of the third tube compared to the pressure at theinlet of the third tube, thus, allowing sucking the thermally balancingliquid through the third tube instead of pressing it into the thirdtube. As described above, this arrangement may help avoiding that thethermally balancing liquid, i.e. the water, the aqueous solution, thenon-aqueous liquid, or the non-aqueous solution, may intrude into thefirst tube and/or the second tube. As a consequence of this embodiment,the lower pressure that may be generated in the liquid flow may, thus,inhibit an intrusion of the thermally balancing liquid into theventilatory circuit which may, otherwise, result in a suffocation of thepatient.

Herein, the mixing chamber may assume any possible form which may besuitable for receiving and mixing the first gas flow and the second gasflow and obtaining enriched respiratory gases comprising the humidifiedaerosol and which has at least one outlet for administering the enrichedrespiratory gases comprising the humidified aerosol. In a particularlypreferred embodiment, the mixing chamber may be identical with thepatient interface, wherein the outlet may be configured foradministering the enriched respiratory gases comprising the humidifiedaerosol to the respiratory track of the patient or to an additionaldevice that may be located between the patient interface and therespiratory track of the patient. In an alternative embodiment, theoutlet of the mixing chamber may be configured for administering theenriched respiratory gases comprising the humidified aerosol to thepatient interface or to an additional device that may be located betweenthe outlet and the patient interface.

For further details with respect to the device reference may be made tothe description of the method and of the exemplary embodiments elsewherein this document.

In a further aspect, the present invention refers to a use of a devicefor administering a humidified aerosol to a patient interface inrespiratory support of preterm infants. As already indicated above,small cross sections, such those which are typically used in respiratorysupport of preterm infants, may, especially, profit from theconsiderably reduced high risk of suffocation which can be achieved bythe device according to the present invention.

Consequently, the method and the device according to the presentinvention may, thus, particularly allow avoiding the administration ofdry or re-dried powdered aerosols. As a result, no unwanted depositionof powdered material which can, finally, lead to a blockage of a tubeor, subsequently, of an airway in the respiratory tract may occur.Advantageously, no obstructions in breathing up to suffocation of thepatient may be due to an absence of such a kind of deposition.Especially, small cross sections, such those which are typically used inrespiratory support of preterm infants, may profit from the considerablyreduced high risk of suffocation. The absence of such unwanteddeposition may render it far easier to determine which exact dose of asubstance to be administered may have actually reached the target organ.

In addition, the mixing of the first gas flow and the second gas flow,which may be provided at different temperatures, at a common temperaturemay, in particular, contribute to the mentioned advantages of thepresent invention. In addition, adjusting the common temperature to atemperature determined for a breath of a patient at least partiallyventilated by the ventilatory circuit may result in an accuratetemperature in the mixing chamber which may, additionally, providesupport for avoiding the redrying of the humidified aerosol, thus,additionally inhibiting a blockage of the patient interface.

SHORT DESCRIPTION OF THE FIGURES

Further optional features and embodiments of the invention will bedisclosed in more detail in the subsequent description of preferredembodiments, preferably in conjunction with the dependent claims.Therein, the respective optional features may be implemented in anisolated fashion as well as in any arbitrary feasible combination, asthe skilled person will realize. It is emphasized that the scope of theinvention may not be restricted by the preferred embodiments. Theembodiments are schematically depicted in the Figures. Therein,identical reference numbers in these Figures refer to identical orfunctionally comparable elements.

In the Figures:

FIGS. 1A and 1B schematically illustrate a profile (FIG. 1A) and a crosssection (FIG. 1B), respectively, of an exemplary device foradministering a humidified aerosol to a patient interface according tothe present invention;

FIGS. 2A and 2B schematically illustrate two different embodiments eachcomprising humidifiers attached to the exemplary device of FIGS. 1A and1B; and

FIGS. 3A and 3B show a comparison between images of cross sections ofpatient interfaces in form of nasal prongs inserted in a holder whichare comparable to those that are, typically, used in respiratory supportof preterm infants for administering a humidified aerosol to the patientinterface without using the method and the device according to thepresent invention (FIG. 3A; state of the art) or by using the method andthe exemplary device according to FIG. 1 or 2, respectively (FIG. 3B).

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1A schematically shows a profile of an exemplary device 110 foradministering a humidified aerosol 112 to a patient interface 114according to the present invention. The device 110 may, in particular,be used for patients, including but not limited to preterm infants, whoare subject to mechanical ventilation or to ventilatory support.

As depicted in FIG. 1A, the exemplary device 110 comprises a first tube116 which is configured according to step a) for receiving and guiding afirst gas flow 118 that comprises the humidified aerosol 112 to a mixingchamber 120. For this purpose, the first gas flow 118 may, preferably,be provided at a first inlet 122 of the first tube 116 at a firsttemperature T₁ and at 100% relative humidity.

As further shown in FIG. 1A, the exemplary device 110 further comprisesa second tube 124 which is configured according to step b) for receivingand guiding a second gas flow 126 that comprises humidified respiratorygases 128 to the mixing chamber 120. Herein, the humidified respiratorygases 128 may comprise a composition which may be suitable forventilation of the patient, in particular, air or oxygen-enriched air.For this purpose, the second gas flow 124 may, preferably, be providedat a second inlet 130 of the second tube 124 at a second temperature T₂but also at 100% relative humidity.

As further illustrated in FIG. 1A, the exemplary device 110 furthercomprises a third tube 132 which is configured according to step c) forreceiving and guiding a liquid flow 134 that comprises a thermallybalancing liquid 136. Herein, the thermally balancing liquid 136 whichrefers to a liquid substance that is, generally, adapted for being usedas a support in achieving a thermal balance between the first gas flow118 and the second gas flow 126. For this purpose, the thermallybalancing liquid 136 may, in particular, be selected from one of wateror an aqueous solution. However, other kinds of liquid substances, suchas a non-aqueous liquid or a non-aqueous solution, may also be feasiblefor this purpose.

Preferably, the third tube 132 may, as further schematically depicted inFIG. 1A, comprise an inlet 138 for receiving the thermally balancingliquid 136 and an outlet 140 for dispensing the thermally balancingliquid 136. In a particularly preferred embodiment, the device 110 mayfurther comprise a pumping unit (not depicted here) which may be adaptedfor applying a pressure p₂ at the outlet 140 of the third tube 132 whichmay be lower compared to the pressure p₁ which may prevail at the inlet138 of the third tube 132. In this manner the liquid flow 134 of thethermally balancing liquid 136 may be guided in a sucking motion throughthe third tube 132 instead of pressing it into the third tube 132. As aresult, the arrangement as shown in FIG. 1A may, thus, help avoidingthat the thermally balancing liquid 136 may intrude into the first tube116 and/or into the second tube 124 and, eventually, into the patientinterface 114 which may, otherwise, result in a suffocation of thepatient.

As further schematically depicted in FIG. 1A, the liquid flow 134 may beapplied in form of a counter flow arrangement in which the liquid flow134 may assume an opposite direction compared to the directions of thefirst flow 118 and of the second flow 126, thus, allowing increasing aneffectivity of the thermal balancing. However, a parallel flow of thefirst gas flow 118, the second gas flow 126 and the liquid flow 134 (notdepicted here) may also be feasible.

Any or, preferably, all of the first tube 116, the second tube 124 andthe third tube 132 may be selected from a rigid tube, such as a pipe,or, preferably, from a semi-rigid or, more preferred, from a flexibletube, such as a hose or a sleeve. By using the flexible tube, the device110 may, advantageously, more easily be adjustable to the requirementsof the patient. In particular, any or, preferably, all of the first tube116, the second tube 124 and the third tube 132 may comprise asubstantially constant cross section along their length, especially, forallowing the first gas flow 118, the second gas flow 126 and/or liquidflow 134 to move in a substantially constant manner through the firsttube 116, thereby reducing a risk of depositions, in particular of theaerosol 112 comprised by the first gas flow 118.

FIG. 1B schematically shows a cross section of the device 110 foradministering the humidified aerosol to the patient interface 114 of thedevice 110 as illustrated in FIG. 1A. As depicted there, the first tube116, the second tube 124 and the third tube 134 are provided in acoaxial arrangement with respect to each other, wherein the third tube132 covers the first tube 116 and the second tube 124. In the exemplaryembodiment as shown here; the first tube 116 has a first axis, thesecond tube 124 has a second axis, and the third tube 132 has a thirdaxis, wherein the first axis, the second axis, and the third axiscoincide with respect to each other, thus, resulting in a triaxialarrangement of the tubes 116, 124, 132. However, other arrangements maystill be feasible.

Returning to FIG. 1A, it is illustrated there that, in accordance withthe present invention, the second gas flow 126 is guided through thesecond tube 124 in a manner that it may at least partially surround thefirst gas flow 116 which is guided through the first tube 116. Thisarrangement may, preferably, be achieved by locating the first tube 116inside the second tube 124, in particular, in a coaxial manner as shownin FIG. 1B. This embodiment may particularly be advantageous when thefirst tube 116 which is configured for receiving and guiding thehumidified aerosol 112 may exhibit a smaller flow volume compared to thesecond tube 124 being configured for receiving and guiding thehumidified respiratory gases 128.

The arrangement as illustrated in FIGS. 1A and 1B, thus, allowsthermally balancing the first gas flow 118 and the second gas flow 126according to step d) by parallel guiding the first gas flow 118 and thesecond gas flow 126. Herein, the first gas flow 118 and the second gasflow 126 may be guided in a manner that they are at least partiallysurrounded by the liquid flow 134 of the thermally balancing liquid 136.For this purpose, the third tube 132 may, preferably, have a form of ajacket or a sheath which may be designated for covering both the secondtube 124 and, consequently, also the first tube 116 which is locatedinside the second tube 124 in the exemplary embodiment of FIGS. 1A and1B. This kind of arrangement may, in particular, allow achieving aneffective cooling of both the first gas flow 118 and the second gas flow126 along their corresponding paths via the first tube 116 and thesecond tube 124 through which they are guided, respectively.

As further illustrated in FIG. 1A, the exemplary device 110 furthercomprises the mixing chamber 120 which, according to step e), isdesigned, on one hand, for receiving the first gas flow 118 from a firstoutlet 146 of the first tube 116 and the second gas flow 126 from asecond outlet 148 of the second tube 124 and, on the other hand, formixing the received first gas flow 118 and the received second gas flow126, whereby enriched respiratory gases 142 which comprise thehumidified aerosol 112, which may, preferably, be distributed across theentire volume of the respiratory gases 128 in a uniform and finelydispersed form, can be generated and provided via one or more outlets150 according to step f).

As schematically depicted in FIG. 1A, the mixing chamber 120 may, inthis particularly preferred embodiment, be identical with the patientinterface 114 which, thus, comprises the outlets 150 for directly orindirectly administering the enriched respiratory gases 142. Herein,additional parts (not depicted here) may, in general, be introducedbetween the patient interface 114 and the respiratory tracks of thepatient. In this particular embodiment, the patient interface 114 may,preferably, be comprise a further outlet 144, the further outlet 144being configured for outputting exhaled gases as received from thepatient.

In an alternative embodiment (not depicted here), the patient interface114 may be attached in form of a separate unit to the outlets 150 of themixing chamber 120. Also here, additional parts may, in general, beintroduced between the mixing chamber 120 and the patient interface 114and/or between the patient interface 114 and the respiratory tracks ofthe patient.

Considering that the first gas flow 118 assumes a third temperature T₃at the first outlet 146 of the first tube 116 and the second gas flow126 assumes a fourth temperature T₄ at the second outlet 148 of thesecond tube 124, the first gas flow 118 and the second gas flow 146 aremixed, preferably, in the mixing chamber 120 at a common temperatureT_(c). In a particularly preferred embodiment, the common temperatureT_(c) may equal both the third temperature T₃ and the fourth temperatureT₄ but, due to cooling of both the first gas flow 118 and the second gasflow 126 along their respective tunes 116, 124, the common temperatureT_(c) may be lower than both the first temperature T₁ at the first inlet12 of the first tube 116 and the second temperature T₂ at the secondinlet 130 of the second tube 124.

In addition to the adjustment of the temperatures as described herein,the first gas flow 118 and the second gas flow 126 may, most preferred,be mixed in accordance with step e) at 100% relative humidity of allparticipating gas glows 118, 126. In order to arrive at thisparticularly preferred embodiment, the thermally balancing of both thefirst gas flow 118 and the second gas flow 126 according to step d) maybe applied in the manner that the humidity and the common temperatureT_(c) in the mixing chamber 120 may assume the mentioned values.

As indicated above, this particularly preferred embodiment may ensurethat practically no accumulation of powdered material may occur, thus,avoiding a blockage of a tube or of an airway in the respiratory tract.In order to further improve this advantage of the present invention, thethermally balancing of both the first gas flow 118 and the second gasflow 126 according to step d) can, additionally, be applied in a mannerthat the common temperature T_(c) may be adjusted to a breathtemperature T_(b), wherein the breath temperature T_(b) may bedetermined for a breath of a patient who is at least partiallyventilated via the patient interface 114. In this regard, a thermometeror a thermocouple may be used for determining the breath temperatureT_(b). In this further improved embodiment any differences between thetemperature of the breath of the actually ventilated patient and thetemperature of the flow of the enriched respiratory gases 142 maydisappear, thus, further contributing to avoiding a deposition in thepatient interface 114.

As illustrated in FIGS. 2A and 2B, the exemplary device 110 may furthercomprise a first humidifier 152 configured to humidify a dry aerosol 154and a second humidifier 156 configured to humidify dry respiratory gases158. As already mentioned above, the term “dry” with respect to the dryaerosol 154 and the dry respiratory gases 158 refers to a condition ofthe aerosol and the respiratory gases which may comprise less than 100%relative humidity, thus, allowing the aerosol and the respiratory gasesto be at least further humidified. Preferably, the dry aerosol 154 maybe humidified prior to step a) and, subsequently, be guided as thehumidified aerosol 112 to the first inlet 122 of the first tube 116 asshown in FIG. 1A. Similarly, the respiratory gases 158 may, preferably,be humidified prior to step b) and, subsequently, be guided as thehumidified respiratory gases 128 to the second inlet 130 of the secondtube 124 as further shown in FIG. 1A.

In the particular embodiments as depicted in FIGS. 2A and 2B, both thefirst humidifier 152 and the second humidifier 156 have been chosen inan arrangement as proposed in WO 2015/132172 A1. Accordingly, thehumidifiers 152, 156 may each have a water compartment 160 comprisingwater which may be designated for humidifying the dry aerosol 154 or thedry respiratory gases 158, respectively. For further details, referencemay be made to WO 2015/132172 A1, which is incorporated here byreference. However, other kinds of humidifiers and alternativearrangements may also be feasible.

FIGS. 3A and 3B provide a comparison between cross sections of airways162 comprised by a nasal prong 164 which is designed for being used asthe patient interface 114 in respiratory support of preterm infants.

As shown in FIG. 3A, administering the humidified aerosol 112 to thepatient interface 114 of the infant in accordance with the state of theart without application of the method and the device 110 according tothe present invention, a considerable degree of unwanted powderedmaterial deposition 166 may lead to a blockage of the airways 162 of thenasal prong 164. As illustrated here, this effect may, especially, bedangerous since it may lead to a high risk of suffocation of the infant.

In contrast hereto, practically no depositions can be observed when thedry aerosol 154 is humidified by applying the method and the device 110for administering the humidified aerosol 112 to the patient interface114 of the infant according to the present invention. Consequently, themethod and the device 110 according to the present invention caneffectively be applied even in this sophisticated case in order to avoidan at least partial redrying of the humidified aerosol 112 on its pathto the patient interface 114.

LIST OF REFERENCE NUMBERS

110 device

112 humidified aerosol

114 patient interface

116 first tube

118 first gas flow

120 mixing chamber

122 first inlet

124 second tube

126 second gas flow

128 humidified respiratory gases

130 second inlet

132 third tube

134 liquid flow

136 thermally balancing liquid

138 inlet

140 outlet

142 enriched respiratory gases

144 further outlet

146 first outlet

148 second outlet

150 outlets

152 first humidifier

154 dry aerosol

156 second humidifier

158 dry respiratory gases

160 water compartment

162 airway

164 nasal prong

166 deposition

1.-16. (canceled)
 17. A method for administering a humidified aerosol toa patient interface, comprising the following steps: a) providing andguiding a first gas flow comprising a humidified aerosol; b) providingand guiding a second gas flow comprising humidified respiratory gases;c) providing and guiding a liquid flow of a thermally balancing liquid;d) thermally balancing the first gas flow and the second gas flow byparallel guiding the first gas flow and the second gas flow, wherein thefirst gas flow and the second gas flow are guided in a manner that theyare at least partially surrounded by the liquid flow of the thermallybalancing liquid; e) mixing the first gas flow and the second gas flow,whereby enriched respiratory gases comprising the humidified aerosol areobtained; and f) administering the enriched respiratory gases comprisingthe humidified aerosol to the patient interface.
 18. The method of claim17, wherein the second gas flow is guided in a manner that it at leastpartially surrounds the first gas flow.
 19. The method of claim 17,wherein the first gas flow is provided pursuant to step a) at a firsttemperature, wherein the second gas flow is provided pursuant to step b)at a second temperature, wherein the first gas flow and the second gasflow are mixed pursuant to step e) at a common temperature, wherein thecommon temperature is lower than the first temperature and the secondtemperature.
 20. The method of claim 19, wherein the common temperatureis adjusted to a temperature determined for a breath of a patient atleast partially ventilated by the ventilatory circuit.
 21. The method ofclaim 17, wherein the first gas flow is provided pursuant to step a) at100% relative humidity, wherein the second gas flow is provided pursuantto step b) at 100% relative humidity, and wherein the first gas flow andthe second gas flow are mixed pursuant to step e) at 100% relativehumidity.
 22. The method of claim 17, wherein the liquid flow of thethermally balancing liquid is guided by applying a lower pressure inflow direction.
 23. The method of claim 17, wherein the thermallybalancing liquid is selected from one of water, an aqueous solution, anon-aqueous liquid, or a non-aqueous solution.
 24. The method of claim17, wherein dry aerosol is humidified prior to step a) and wherein dryrespiratory gases are humidified prior to step b).
 25. The method ofclaim 17, wherein the humidified aerosol is administered in respiratorysupport of preterm infants.
 26. A device for administering a humidifiedaerosol to a patient interface, comprising: at least one first tube forreceiving and guiding a first gas flow comprising a humidified aerosol;at least one second tube for receiving and guiding a second gas flowcomprising humidified respiratory gases; at least one third tube forreceiving and guiding a liquid flow comprising a thermally balancingliquid; wherein the first tube, the second tube and the third tube areprovided in a coaxial arrangement with respect to each other, whereinthe third tube covers the first tube and the second tube; and at leastone mixing chamber for receiving and mixing the first gas flow and thesecond gas flow and obtaining enriched respiratory gases comprising thehumidified aerosol, the mixing chamber having at least one outlet foradministering the enriched respiratory gases comprising the humidifiedaerosol.
 27. The device of claim 26, wherein the first tube is locatedinside the second tube.
 28. The device of claim 26, wherein the thirdtube forms a jacket directly or indirectly covering the first tube andthe second tube.
 29. The device of claim 26, wherein the first tube hasa first axis, the second tube has a second axis, and the third tube hasa third axis, wherein the first axis, the second axis, and the thirdaxis coincide with respect to each other.
 30. The device of claim 26,wherein the third tube comprises at least one inlet for receiving thethermally balancing liquid and at least one outlet for dispensing thethermally balancing liquid, wherein the device further comprises apumping unit being designed for applying a lower pressure at the outletcompared to the pressure at the inlet.
 31. The device of claim 26,wherein at least one of the first tube, the second tube and the thirdtube is a flexible tube.
 32. The device of claim 26, wherein at leastone of the first tube, the second tube and the third tube comprises aconstant cross section along their length.
 33. The device of claim 26,further comprising at least one first humidifier configured to humidifydry aerosol and at least one second humidifier configured to humidifydry respiratory gases.